SAN CARLOS, Calif., Nov. 14 /PRNewswire-FirstCall/ -- Nuvelo, Inc. today announced that final results from a Phase 2a dose-escalating trial showing that recombinant nematode anticoagulant protein c2 (rNAPc2) has an acceptable safety profile and is well tolerated in doses up to 10 micrograms/kg in patients being treated for acute coronary syndromes (ACS). Results of the randomized, double-blind study, known as ANTHEM (Anticoagulation with rNAPc2 To Help Eliminate Major Adverse Cardiac Events)/TIMI 32, were presented in a poster session today at the American Heart Association’s Scientific Sessions 2005 in Dallas. rNAPc2 is a novel anti-coagulant currently being studied in a Phase 2 proof of concept clinical trial as a potential replacement for heparin in patients being treated for ACS.
ACS accounts for more than 1 million hospitalizations annually in the United States. It occurs when an atherosclerotic plaque ruptures in a coronary artery, triggering the coagulation cascade, which results in the formation of a blood clot. The clot blocks the flow of blood to the heart muscle, depriving it of oxygen, which can result in unstable angina or heart attack.
“Improved antithrombotic therapies are needed for the treatment of ACS because high rates of heart attack and death occur in the first month after ACS despite intensive therapy with the current standard of care, which includes antithrombotics and early catheterization,” said presenter Robert P. Giugliano, M.D., S.M., investigator, TIMI Study Group; associate physician, Brigham and Women’s Hospital and assistant professor of Medicine, Harvard Medical School. “The results of this Phase 2a study of rNAPc2 in ACS are encouraging and warrant further evaluation to determine if rNAPc2 improves clinical outcomes.”
Phase 2a Study Design and Results
The Phase 2a multi-center, double-blind, placebo-controlled, ascending dose-escalation study was conducted by the TIMI Group, led by Eugene Braunwald, M.D., distinguished Hersey professor of medicine at Harvard Medical School and chairman of the TIMI Study Group at Brigham and Women’s Hospital and completed enrollment in May 2005. The trial investigated the safety of rNAPc2 in combination with other antithrombotics in 203 patients with ACS who were age 18 to 75. The study consisted of a dose-ranging phase and a dose-confirmation phase. The primary focus of dose ranging was to identify a well tolerated dose in combination with other standard antithrombotic agents. In the dose-confirmation phase, 25 patients received 10 micrograms/kg, the highest safe and active dose evaluated, compared with placebo in a 4:1 randomization. All patients received aspirin and low molecular weight heparin or unfractionated heparin. The primary safety endpoint was major or minor bleeding as defined by TIMI criteria, and the primary efficacy endpoints were F1+2 concentration, a measure of new thrombin generation; pro-thrombin time, the time it takes plasma to clot after addition of tissue factor; and pharmacokinetic data.
Results showed that that treatment with rNAPc2, in addition to standard antithrombotic therapies in patients with ACS, resulted in a dose-related inhibition of thrombin generation without an increase in clinically significant bleeding. The TIMI major or minor bleed rate was not statistically different between the two treatment groups (4.3 percent in patients treated with rNAPc2 versus 2.5 percent in those treated with placebo). In addition, rNAPc2 suppressed F1+2 and prolonged the prothrombin time, both in a dose-related fashion.
“We are pleased by the results of the Phase 2a study, which demonstrated that rNAPc2 had an excellent bleeding profile across a wide range of doses including the highest dose tested, 10 micrograms/kg, in patients being treated for ACS,” said Steven R. Deitcher, M.D., vice president, medical affairs for Nuvelo. “We are currently conducting a Phase 2 heparin replacement study, which should give us further indication of the antithrombotic activity of rNAPc2 and its potential ability to replace heparin in ACS. Nuvelo is committed to the clinical development of rNAPc2 because we believe its novel mechanism of action, based on its ability to inhibit the initiation of the coagulation cascade and prevent the formation of blood clots, offers the potential to help patients with ACS and suggests that it may have therapeutic utility in a variety of other indications.”
The Phase 2 heparin replacement study, also known as ANTHEM/TIMI 32, is an open-label study that is evaluating the efficacy and safety of rNAPc2 by reducing the dose of, and ultimately replacing, unfractionated heparin in patients being treated for ACS. The study will include from 50 to 100 patients and is being conducted in approximately 25 centers across the United States and Canada with the TIMI Study Group.
AHA Abstract #2095/C16
Giugliano RP, Wiviott SD, Morrow DA, Simon DI, Schweiger MJ, Chandra M, Deitcher S, Skene A and Braunwald E on behalf of the ANTHEM-TIMI 32 Investigators. “Addition of a Tissue-Factor/Factor VIIa Inhibitor to Standard Treatments in NSTE-ACS Managed with an Early Invasive Strategy: Results of the Phase 2 ANTHEM-TIMI 32 Double-Blind Randomized Clinical Trial.” The abstract will be presented in a poster presentation at the American Heart Association’s Scientific Sessions 2005 on November 14, 2005, in Dallas.
About rNAPc2
A novel antithrombotic, rNAPc2 is a naturally occurring protein that was originally isolated from the hematophageous nematode hookworm, Anclyostoma caninum. The anticoagulant effect of rNAPc2 results from its ability to block the factor VIIa/tissue factor protease complex, which is responsible for the initiation of the process leading to blood clot formation. Unlike heparin, thrombin inhibitors and other agents that exert their effects at later stages of the blood coagulation cascade, rNAPc2 blocks the first step in the cascade, essentially inhibiting coagulation before it starts.
About Nuvelo
Nuvelo, Inc. is dedicated to improving the lives of patients through the discovery, development and commercialization of novel drugs for acute cardiovascular and cancer therapy. Nuvelo’s clinical pipeline includes alfimeprase, a direct-acting thrombolytic in Phase 3 trials for the treatment of acute peripheral arterial occlusion (PAO) and catheter occlusion, and rNAPc2, an antithrombotic currently in Phase 2 trials that inhibits the factor VIIa and tissue factor complex. In addition, Nuvelo has identified NU206 as a preclinical development candidate for the potential treatment of gastrointestinal mucositis from its proprietary research programs and expects to leverage expertise in secreted proteins and antibody discovery to expand its pipeline and create partnering and licensing opportunities.
Information about Nuvelo is available at our website at www.nuvelo.com or by phoning 650-517-8000.
NOTE: This press release contains “forward-looking statements” regarding Nuvelo’s Phase 2 clinical trial of rNAPc2 to treat patients with acute coronary syndromes. The timing and progress of Nuvelo’s Phase 2 program, and the potential improvement or benefit that current clinical trial programs may demonstrate which statements are hereby identified as “forward-looking statements” for purposes of the safe harbor provided by the Private Securities Litigation Reform Act of 1995. Such statements are based on our management’s current expectations and involve risks and uncertainties. Actual results and performance could differ materially from those projected in the forward looking statements as a result of many factors, including, without limitation, uncertainties relating to drug discovery; clinical development processes; enrollment rates for patients in our clinical trials; changes in relationships with strategic partners and dependence upon strategic partners for the performance of critical activities under collaborative agreements; the impact of competitive products and technological changes; uncertainties relating to patent protection and uncertainties relating to our ability to obtain funding. These and other factors are identified and described in more detail in Nuvelo filings with the SEC, including without limitation Nuvelo’s recent annual report on Form 10-K for the year ended December 31, 2004 and subsequent filings. We disclaim any intent or obligation to update these forward-looking statements.
Nuvelo, Inc.
CONTACT: Nicole Estrin, Associate Director of Corporate Communications &IR of Nuvelo, Inc., +1-650-517-8472, or nestrin@nuvelo.com; or CarolynBumgardner Wang of WeissComm Partners, Inc., +1-415-946-1065, orcarolyn@weisscommpartners.com, for Nuvelo, Inc.
Web site: http://www.nuvelo.com/
